Cell and Tissue Research

, Volume 305, Issue 3, pp 399–409

Dynamic changes in protein components of the tight junction during liver regeneration

  • Yasuyuki Takaki
  • Syu-ichi Hirai
  • Naoyuki Manabe
  • Yasushi Izumi
  • Tomonori Hirose
  • Masa-aki Nakaya
  • Atsushi Suzuki
  • Keiko Mizuno
  • Kazunori Akimoto
  • Shoichiro Tsukita
  • Taro Shuin
  • Shigeo Ohno
Regular article

DOI: 10.1007/s004410100397

Cite this article as:
Takaki, Y., Hirai, S., Manabe, N. et al. Cell Tissue Res (2001) 305: 399. doi:10.1007/s004410100397

Abstract.

The construction of the hepatocyte tight junction is one of the most important events during liver regeneration leading to the reorganization of the bile canaliculi and the repolarization of hepatocytes after cell division. To understand this event at the molecular level, we examined the expression of tight junction proteins by Western blot analysis and their cellular localization by immunofluorescence microscopy in regenerating rat liver after two-thirds hepatectomy. The levels of tight junction components such as claudin-3, ZO-1 and atypical protein kinase C (PKC)-specific interacting protein (ASIP) increased two- to three-fold over control levels in coordination with a peak 2–3 days after partial hepatectomy, whereas occludin levels remained unchanged. The bile canaliculi outlined by tight junction components and actin filaments reveal significant morphological changes from 2–3 days after partial hepatectomy. During this period, claudin-3/ZO-1 and ASIP/ZO-1 were nearly co-localized, whereas occludin was locally reduced or almost absent on the bile canaliculi outlined by ZO-1 staining. The uncoupled localization of F-actin and tight junction components was often observed. The function of hepatocytes, as revealed by the serum bile acids level, was distorted temporally at an early stage of regeneration but mostly restored 3 days after partial hepatectomy. These observations suggest that the de novo construction of tight junctions proceeds mainly 2–3 days after partial hepatectomy in parallel with the cell polarization required for hepatocyte function. However, the complete normalization of the composition of the tight junction components, such as occludin and the association with F-actin, requires additional time, which may support the regeneration of fully polarized normal hepatocytes.

Hepatocyte Tight junction Claudin-3 ASIP aPKC ZO-1 Occludin Rat (Sprague Dawley)

Copyright information

© Springer-Verlag 2001

Authors and Affiliations

  • Yasuyuki Takaki
    • 1
  • Syu-ichi Hirai
    • 1
  • Naoyuki Manabe
    • 1
  • Yasushi Izumi
    • 1
  • Tomonori Hirose
    • 1
  • Masa-aki Nakaya
    • 1
  • Atsushi Suzuki
    • 1
  • Keiko Mizuno
    • 1
  • Kazunori Akimoto
    • 1
  • Shoichiro Tsukita
    • 3
  • Taro Shuin
    • 2
  • Shigeo Ohno
    • 1
  1. 1.Department of Molecular Biology, Yokohama City University School of Medicine, Kanazawa-ku, Yokohama 236–0004, Japan
  2. 2.Department of Urology, Kochi Medical School, Nankoku, Kochi 783–8505, Japan
  3. 3.Department of Cell Biology, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto 606–01, Japan